Variant 8-139618747-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001282534.2(KCNK9):c.636T>C(p.Gly212=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 1,613,930 control chromosomes in the GnomAD database, including 341,767 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.70 ( 37437 hom., cov: 32)

Exomes 𝑓: 0.64 ( 304330 hom. )

Consequence

KCNK9
NM_001282534.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:3

Conservation

PhyloP100: -0.891

Variant links:

Genes affected

KCNK9 (HGNC:6283): (potassium two pore domain channel subfamily K member 9) This gene encodes a protein that contains multiple transmembrane regions and two pore-forming P domains and functions as a pH-dependent potassium channel. Amplification and overexpression of this gene have been observed in several types of human carcinomas. This gene is imprinted in the brain, with preferential expression from the maternal allele. A mutation in this gene was associated with Birk-Barel dysmorphism syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2017]

KCNK9 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 8-139618747-A-G is Benign according to our data. Variant chr8-139618747-A-G is described in ClinVar as [Benign]. Clinvar id is 1174840.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-139618747-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.891 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNK9	NM_001282534.2 linkuse as main transcript	c.636T>C	p.Gly212=	synonymous_variant	2/2	ENST00000520439.3
KCNK9	NR_104210.2 linkuse as main transcript	n.767T>C		non_coding_transcript_exon_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNK9	ENST00000520439.3 linkuse as main transcript	c.636T>C	p.Gly212=	synonymous_variant	2/2	1	NM_001282534.2	P1

Frequencies

GnomAD3 genomes

AF:

0.695

AC:

105579

AN:

151944

Hom.:

37385

Cov.:

show subpopulations

Gnomad AFR

AF:

0.848

Gnomad AMI

AF:

0.488

Gnomad AMR

AF:

0.675

Gnomad ASJ

AF:

0.555

Gnomad EAS

AF:

0.690

Gnomad SAS

AF:

0.627

Gnomad FIN

AF:

0.641

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.630

Gnomad OTH

AF:

0.692

GnomAD3 exomes

AF:

0.656

AC:

164883

AN:

251280

Hom.:

54702

AF XY:

0.646

AC XY:

87810

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.854

Gnomad AMR exome

AF:

0.695

Gnomad ASJ exome

AF:

0.562

Gnomad EAS exome

AF:

0.689

Gnomad SAS exome

AF:

0.619

Gnomad FIN exome

AF:

0.643

Gnomad NFE exome

AF:

0.632

Gnomad OTH exome

AF:

0.646

GnomAD4 exome

AF:

0.643

AC:

940567

AN:

1461868

Hom.:

304330

Cov.:

AF XY:

0.641

AC XY:

466296

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.857

Gnomad4 AMR exome

AF:

0.692

Gnomad4 ASJ exome

AF:

0.560

Gnomad4 EAS exome

AF:

0.702

Gnomad4 SAS exome

AF:

0.618

Gnomad4 FIN exome

AF:

0.643

Gnomad4 NFE exome

AF:

0.637

Gnomad4 OTH exome

AF:

0.646

GnomAD4 genome

AF:

0.695

AC:

105688

AN:

152062

Hom.:

37437

Cov.:

AF XY:

0.692

AC XY:

51424

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.848

Gnomad4 AMR

AF:

0.675

Gnomad4 ASJ

AF:

0.555

Gnomad4 EAS

AF:

0.690

Gnomad4 SAS

AF:

0.627

Gnomad4 FIN

AF:

0.641

Gnomad4 NFE

AF:

0.630

Gnomad4 OTH

AF:

0.693

Alfa

AF:

0.650

Hom.:

41878

Bravo

AF:

0.707

Asia WGS

AF:

0.695

AC:

2415

AN:

3478

EpiCase

AF:

0.626

EpiControl

AF:

0.624

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.3

DANN

Benign

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over